tbuckley/cabot-search huggingface dataset:
Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection
Authors: William M. Garneau, Kimberly Jones-Beatty, Michelle O. Ufua, Heba H. Mostafa, Sabra L. Klein, Irina Burd, Kelly A. Gebo
Journal: JAMA Network Open (2022)

Importance Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available. Objective To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients. Design, Setting, and Participants This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022. Exposures Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures Clinical characteristics and outcomes were ascertained through manual record review. Results Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities. Conclusions and Relevance In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.
Commentary on “Dysfunctional dendritic cells limit antigen-specific T cell response in glioma”
Authors: Robert M Prins, Richard G Everson
Journal: Neuro-Oncology (2022)

Journal Article Commentary on "Dysfunctional dendritic cells limit antigen-specific T cell response in glioma" Get access Robert M Prins, Robert M Prins Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAParker Institute for Cancer Immunotherapy, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA Corresponding Author: Robert M. Prins, PhD, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA (rprins@mednet.ucla.edu). https://orcid.org/0000-0002-6282-6583 Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard G Everson Richard G Everson Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USAJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 2, February 2023, Pages 277–278, https://doi.org/10.1093/neuonc/noac256 Published: 29 November 2022 Article history Published: 29 November 2022 Corrected and typeset: 27 December 2022
Hippocampal representations of foraging trajectories depend upon spatial context
Authors: Wan-Chen Jiang, Shengjin Xu, Joshua T. Dudman
Journal: Nature Neuroscience (2022)

Abstract Animals learn trajectories to rewards in both spatial, navigational contexts and relational, non-navigational contexts. Synchronous reactivation of hippocampal activity is thought to be critical for recall and evaluation of trajectories for learning. Do hippocampal representations differentially contribute to experience-dependent learning of trajectories across spatial and relational contexts? In this study, we trained mice to navigate to a hidden target in a physical arena or manipulate a joystick to a virtual target to collect delayed rewards. In a navigational context, calcium imaging in freely moving mice revealed that synchronous CA1 reactivation was retrospective and important for evaluation of prior navigational trajectories. In a non-navigational context, reactivation was prospective and important for initiation of joystick trajectories, even in the same animals trained in both contexts. Adaptation of trajectories to a new target was well-explained by a common learning algorithm in which hippocampal activity makes dissociable contributions to reinforcement learning computations depending upon spatial context.
Associating Immunotherapy and Targeted Therapies: Facts and Hopes
Authors: Sylvain Ladoire, Cédric Rébé, François Ghiringhelli
Journal: Clinical Cancer Research (2022)

Abstract Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1/PD-L1 (Programmed Death 1/Programmed Death-Ligand 1) axis, have modified the management of many types of cancer over the last 10 years. However, both intrinsic and acquired resistance are major clinical issues with these therapies, and only a few patients are cured by ICI monotherapy. To overcome resistance, the concept of combining ICIs with other therapies is emerging and supported by many preclinical trials. Besides associations of ICIs with chemotherapy or radiotherapy, now used in clinical practice, some targeted therapies have also been reported to influence immune response of patients against cancer cells, thus showing potential synergy with ICIs. In this review, we describe the preclinical and clinical advances to date in the use of these combination strategies.
Distinct serotonergic pathways to the amygdala underlie separate behavioral features of anxiety
Authors: Xiao-Dan Yu, Yi Zhu, Qi-Xin Sun, Fei Deng, Jinxia Wan, Di Zheng, Wankun Gong, Shi-Ze Xie, Chen-Jie Shen, Jia-Yu Fu, Huiqian Huang, Hsin-Yi Lai, Jin Jin, Yulong Li, Xiao-Ming Li
Journal: Nature Neuroscience (2022)
IFN-γR/STAT1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease
Authors: Caisheng Lu, Huihui Ma, Liangsong Song, Hui Wang, Lily Wang, Shirong Li, Stephen M. Lagana, Antonia R. Sepulveda, Kasper Hoebe, Samuel S. Pan, Yong-Guang Yang, Suzanne Lentzsch, Markus Y. Mapara
Journal: Journal of Clinical Investigation (2022)

The absence of IFN-γ receptor (IFN-γR) or STAT1 signaling in donor cells has been shown to result in reduced induction of acute graft-versus-host disease (GVHD). In this study, we unexpectedly observed increased activation and expansion of donor lymphocytes in both lymphohematopoietic organs and GVHD target tissues of IFN-γR/STAT1-deficient recipient mice, leading to rapid mortality following the induction of GVHD. LPS-matured, BM-derived Ifngr1-/- Stat1-/- DCs (BMDCs) were more potent allogeneic stimulators and expressed increased levels of MHC II and costimulatory molecules. Similar effects were observed in human antigen-presenting cells (APCs) with knockdown of Stat1 by CRISPR/Cas9 and treatment with a JAK1/2 inhibitor. Furthermore, we demonstrated that the absence of IFN-γR/STAT1 signaling in hematopoietic APCs impaired the presentation of exogenous antigens, while promoting the presentation of endogenous antigens. Thus, the indirect presentation of host antigens to donor lymphocytes was defective in IFN-γR/STAT1-deficient, donor-derived APCs in fully donor chimeric mice. The differential effects of IFN-γR/STAT1 signaling on endogenous and exogenous antigen presentation could provide further insight into the roles of the IFN-γ/STAT1 signaling pathway in the pathogenesis of GVHD, organ rejection, and autoimmune diseases.
A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC
Authors: Laurel B. Darragh, Michael M. Knitz, Junxiao Hu, Eric T. Clambey, Jennifer Backus, Andrew Dumit, Von Samedi, Andrew Bubak, Casey Greene, Timothy Waxweiler, Sanjana Mehrotra, Shilpa Bhatia, Jacob Gadwa, Thomas Bickett, Miles Piper, Kareem Fakhoury, Arthur Liu, Joshua Petit, Daniel Bowles, Ashesh Thaker, Kimberly Atiyeh, Julie Goddard, Robert Hoyer, Adrie Van Bokhoven, Kimberly Jordan, Antonio Jimeno, Angelo D’Alessandro, David Raben, Jessica D. McDermott, Sana D. Karam
Journal: Nature Cancer (2022)

Abstract Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly ( n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.
A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair
Authors: Zhiyuan Wang, Shuaijun Jia, Hailiang Xu, Xiaohui Wang, Botao Lu, Weidong Wu, Dageng Huang, Lingbo Kong, Xin Kang, Fang Tian, Lei Zhu, Dingjun Hao
Journal: Theranostics (2022)

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs.Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment.Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro.However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency.Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results:We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs.The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain.In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin β1/GSK3β/β-catenin signaling pathway.Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation.Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion:The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.
Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway: Erratum
Authors: Hui-Juan Liu, Yuan Qin, Zi-Han Zhao, Yang Zhang, Jia-Huan Yang, Deng-Hui Zhai, Fang Cui, Ce Luo, Man-Xi Lu, Piao-Piao Liu, Heng-Wei Xu, Kun Li, Bo Sun, Shuang Chen, Hong-Gang Zhou, Cheng Yang, Tao Sun
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.46467.].
Biomineralized Bimetallic Oxide Nanotheranostics for Multimodal Imaging-Guided Combination Therapy: Erratum
Authors: Jianrong Wu, Gareth R. Williams, Shiwei Niu, Yanbo Yang, Yu Li, Xuejing Zhang, Li-Min Zhu
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.40715.].
Highly sensitive magnetic particle imaging of vulnerable atherosclerotic plaque with active myeloperoxidase-targeted nanoparticles
Authors: Wei Tong, Hui Hui, Wenting Shang, Yingqian Zhang, Feng Tian, Qiang Ma, Xin Yang, Jie Tian, Yundai Chen
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.49812.].
Focused ultrasound-augmented targeting delivery of nanosonosensitizers from homogenous exosomes for enhanced sonodynamic cancer therapy: Erratum
Authors: Yichen Liu, Lianmei Bai, Kaili Guo, Yali Jia, Kun Zhang, Quanhong Liu, Pan Wang, Xiaobing Wang
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.33183.].
Excretable IR-820 for <i>in vivo</i> NIR-II fluorescence cerebrovascular imaging and photothermal therapy of subcutaneous tumor: Erratum
Authors: Zhe Feng, Xiaoming Yu, Minxiao Jiang, Liang Zhu, Yi Zhang, Wei Yang, Wang Xi, Gonghui Li, Jun Qian
Journal: Theranostics (2022)

[This corrects the article DOI: 10.7150/thno.31332.].
Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)
Authors: Florence Tydeman, Paul E Pfeffer, Giulia Vivaldi, Hayley Holt, Mohammad Talaei, David Jolliffe, Gwyneth Davies, Ronan A Lyons, Christopher Griffiths, Frank Kee, Aziz Sheikh, Seif O Shaheen, Adrian R Martineau
Journal: Thorax (2022)

Background The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. Methods We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. Results Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p&lt;0.001), increased frequency of indoor visits to public places and other households (p&lt;0.001) and rising incidence of COVID-19 (p&lt;0.001), non-COVID-19 ARI (p&lt;0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). Conclusions Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant. Study registration number NCT04330599 .
Commentary
Authors: Andrei Voiosu
Journal: Endoscopy (2022)

Faced with colonic angioectasia, especially with multiple lesions, we tend to reach for the argon plasma coagulation (APC) probe. However its variable depth penetration and effectiveness give rise to concerns about potential complications and recurrence. Geyl et al. [1] nicely illustrate a previously described technique, focused on treating the deeper submucosal origin of these vascular lesions. Whereas APC treats by spreading from the surface to the deeper layers, resection of the mucosal “cap” centered on the angioectasia reveals the true culprit – larger submucosal feeding vessels, which can then be approached directly ([Fig. 1]). Logically, exposing the submucosa and delivering highly targeted treatment should improve cure rates. Nevertheless, one is left to wonder whether resection, as the authors ask in the title of their E-Video, is indeed “optimal,” especially when a multitude of lesions is encountered. Complications due to APC are rare and not always clinically relevant. But while APC is a “point-and-shoot” technique, the expertise needed for submucosal treatment of the bleeding caused by resection is altogether different. Footing the bill for injection needle, snare, coagulation forceps, and clips might also make one cautious about this otherwise attractive treatment option.
Endoscopy International Open – recently published
Journal: Endoscopy (2022)

Comment on: Single-use duodenoscopes are an efficient tool for emergency ERCP in real lifeEndosc Int Open 2022; 10(11): E1497-E1500DOI: 10.1055/a-1921-2109 Comment on: Artificial intelligence in gastroenterology: Where are we heading?Endosc Int Open 2022; 10(11): E1474-E1480DOI: 10.1055/a-1907-6569 Comment on: Complication rates of direct puncture and pull-through techniques for percutaneous endoscopic gastrostomy: Results from a large multicenter cohortEndosc Int Open 2022; 10(11): E1454-E1461DOI: 10.1055/a-1924-3525
Albumin-hitchhiking: Fostering the pharmacokinetics and anticancer therapeutics
Authors: Paras Famta, Saurabh Shah, Naitik Jain, Dadi A. Srinivasarao, Aditya Murthy, Tausif Ahmed, Ganesh Vambhurkar, Syed Shahrukh, Shashi Bala Singh, Saurabh Srivastava
Journal: Journal of Controlled Release (2022)
Designing Cancer Immunotherapies That Engage T Cells and NK Cells
Authors: Oleksandr Kyrysyuk, Kai W. Wucherpfennig
Journal: Annual Review of Immunology (2022)

T cells and natural killer (NK) cells have complementary roles in tumor immunity, and dual T cell and NK cell attack thus offers opportunities to deepen the impact of immunotherapy. Recent work has also shown that NK cells play an important role in recruiting dendritic cells to tumors and thus enhance induction of CD8 T cell responses, while IL-2 secreted by T cells activates NK cells. Targeting of immune evasion mechanisms from the activating NKG2D receptor and its MICA and MICB ligands on tumor cells offers opportunities for therapeutic intervention. Interestingly, T cells and NK cells share several important inhibitory and activating receptors that can be targeted to enhance T cell– and NK cell–mediated immunity. These inhibitory receptor-ligand systems include CD161-CLEC2D, TIGIT-CD155, and NKG2A/CD94-HLA-E. We also discuss emerging therapeutic strategies based on inhibitory and activating cytokines that profoundly impact the function of both lymphocyte populations within tumors.
Chronic lymphocytic leukemia treatment algorithm 2022
Authors: Paul J. Hampel, Sameer A. Parikh
Journal: Blood Cancer Journal (2022)

Abstract The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as Bruton tyrosine kinase inhibitors and venetoclax) and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in patients with CLL, even among those with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain ( IGHV ) genes. Selecting the right treatment for the right patient requires consideration of disease characteristics and prior treatment sequence, as well as patient preferences and comorbidities. The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts. This review summarizes our current approach to the management of CLL, right from the time of diagnosis through relapsed disease.
Factorizer: A scalable interpretable approach to context modeling for medical image segmentation
Authors: Pooya Ashtari, Diana M. Sima, Lieven De Lathauwer, Dominique Sappey-Marinier, Frederik Maes, Sabine Van Huffel
Journal: Medical Image Analysis (2022)

Convolutional Neural Networks (CNNs) with U-shaped architectures have dominated medical image segmentation, which is crucial for various clinical purposes. However, the inherent locality of convolution makes CNNs fail to fully exploit global context, essential for better recognition of some structures, e.g., brain lesions. Transformers have recently proven promising performance on vision tasks, including semantic segmentation, mainly due to their capability of modeling long-range dependencies. Nevertheless, the quadratic complexity of attention makes existing Transformer-based models use self-attention layers only after somehow reducing the image resolution, which limits the ability to capture global contexts present at higher resolutions. Therefore, this work introduces a family of models, dubbed Factorizer, which leverages the power of low-rank matrix factorization for constructing an end-to-end segmentation model. Specifically, we propose a linearly scalable approach to context modeling, formulating Nonnegative Matrix Factorization (NMF) as a differentiable layer integrated into a U-shaped architecture. The shifted window technique is also utilized in combination with NMF to effectively aggregate local information. Factorizers compete favorably with CNNs and Transformers in terms of accuracy, scalability, and interpretability, achieving state-of-the-art results on the BraTS dataset for brain tumor segmentation and ISLES'22 dataset for stroke lesion segmentation. Highly meaningful NMF components give an additional interpretability advantage to Factorizers over CNNs and Transformers. Moreover, our ablation studies reveal a distinctive feature of Factorizers that enables a significant speed-up in inference for a trained Factorizer without any extra steps and without sacrificing much accuracy. The code and models are publicly available at https://github.com/pashtari/factorizer.